Dose Reduction Research Articles

Ocular adverse events associated with antibody-drug conjugates for cancer: evidence and management strategies.

Antibody-drug conjugates (ADCs) are a fast-growing class of cancer drugs designed to selectively deliver cytotoxic payloads through antibody binding to cancer cells with high expression of the target antigen, thus reducing systemic exposure and minimizing off-target effects. However, ADCs are associated with various ocular adverse events (AEs) that may impact treatment administration and patient outcomes. In this review, we provide a summary of ocular AEs associated with approved and investigational ADCs, recommendations for the mitigation and management of ocular AEs, current guidelines and expert opinions, and recommendations for clinical practice. A literature search was performed, using PubMed and Google Scholar, for English-language articles published between January 1985 and January 2023 to identify studies reporting ocular AEs associated with ADC use. Search terms included generic and investigational names of all identified ADCs, and further searches were performed to identify strategies for managing ADC-associated ocular AEs. ADC-associated ocular AEs include symptoms such as blurred vision and foreign-body sensation and signs such as corneal fluorescein staining, corneal pseudomicrocysts, and conjunctivitis. Reported management strategies include ADC dose modification (eg, dose delay or reduction), cool compresses, artificial tears, topical vasoconstrictors, and topical steroids. Although ADC dose modification appears to be beneficial, the preventive and/or therapeutic benefits of the remaining interventions are unclear. Although the exact mechanisms are not fully understood, most ADC-associated ocular AEs are reversible with dose delay or dose reduction. Management of ocular AEs requires a multidisciplinary approach to minimize treatment discontinuation and optimize clinical outcomes.

Low-contrast lesion detection in neck CT: a multireader study comparing deep learning, iterative, and filtered back projection reconstructions using realistic phantoms

BackgroundComputed tomography (CT) reconstruction algorithms can improve image quality, especially deep learning reconstruction (DLR). We compared DLR, iterative reconstruction (IR), and filtered back projection (FBP) for lesion detection in neck CT.MethodsNine patient-mimicking neck phantoms were examined with a 320-slice scanner at six doses: 0.5, 1, 1.6, 2.1, 3.1, and 5.2 mGy. Each of eight phantoms contained one circular lesion (diameter 1 cm; contrast -30 HU to the background) in the parapharyngeal space; one phantom had no lesions. Reconstruction was made using FBP, IR, and DLR. Thirteen readers were tasked with identifying and localizing lesions in 32 images with a lesion and 20 without lesions for each dose and reconstruction algorithm. Receiver operating characteristic (ROC) and localization ROC (LROC) analysis were performed.ResultsDLR improved lesion detection with ROC area under the curve (AUC) 0.724 ± 0.023 (mean ± standard error of the mean) using DLR versus 0.696 ± 0.021 using IR (p = 0.037) and 0.671 ± 0.023 using FBP (p < 0.001). Likewise, DLR improved lesion localization, with LROC AUC 0.407 ± 0.039 versus 0.338 ± 0.041 using IR (p = 0.002) and 0.313 ± 0.044 using FBP (p < 0.001). Dose reduction to 0.5 mGy compromised lesion detection in FBP-reconstructed images compared to doses ≥ 2.1 mGy (p ≤ 0.024), while no effect was observed with DLR or IR (p ≥ 0.058).ConclusionDLR improved the detectability of lesions in neck CT imaging. Dose reduction to 0.5 mGy maintained lesion detectability when denoising reconstruction was used.Relevance statementDeep learning enhances lesion detection in neck CT imaging compared to iterative reconstruction and filtered back projection, offering improved diagnostic performance and potential for x-ray dose reduction.Key PointsLow-contrast lesion detectability was assessed in anatomically realistic neck CT phantoms.Deep learning reconstruction (DLR) outperformed filtered back projection and iterative reconstruction.Dose has little impact on lesion detectability against anatomical background structures.Graphical

Association between body composition phenotypes and treatment toxicity in women with cervical cancer undergoing chemoradiotherapy

ObjectiveTo identify whether there is an association between body composition phenotypes and toxicity to chemoradiotherapy in women with cervical cancer. MethodsThis is a prospective cohort study that included 330 adult patients with cervical cancer treated with chemoradiotherapy. Computed tomography images were used to assess skeletal muscle index (SMI) and radiodensity (SMD), total adipose tissue index, and visceral adipose tissue index. Chemoradiotherapy toxicity was assessed weekly, and toxicity-induced modification of treatment (TIMT) was considered as any severe adverse event resulting in treatment interruption, delay, or dose reduction. ResultsApproximately 45% of the patients presented at least one unfavorable body composition parameter (lower SMI, lower SMD, higher total adipose tissue index, or higher visceral adipose tissue index), 23% had two conditions, and 3% had three conditions. The incidence of toxicity ≥ grade 3 and TIMT was 55% and 30%, respectively. For adverse events ≥ grade 3, lower SMI was the determining factor for worse outcomes when evaluated alone or combined with lower SMD and normal adiposity. All body composition phenotypes were associated with TIMT, increasing the risk when both conditions were present. ConclusionsLower SMI was an independent factor for the higher number of adverse events, as it remained a risk factor when analyzed in isolation or in association with adipose tissue. Women with excess adipose tissue associated with lower muscle mass had a risk approximately 4 times higher of delaying or interrupting chemoradiotherapy. Furthermore, for the sum of unfavorable conditions, there was a progressive increase in the risk of TIMT.

Improving image quality and in-stent restenosis diagnosis with high-resolution "double-low" coronary CT angiography in patients after percutaneous coronary intervention.

This study aims to investigate the image quality of a high-resolution, low-dose coronary CT angiography (CCTA) with deep learning image reconstruction (DLIR) and second-generation motion correction algorithms, namely, SnapShot Freeze 2 (SSF2) algorithm, and its diagnostic accuracy for in-stent restenosis (ISR) in patients after percutaneous coronary intervention (PCI), in comparison with standard-dose CCTA with high-definition mode reconstructed by adaptive statistical iterative reconstruction Veo algorithm (ASIR-V) and the first-generation motion correction algorithm, namely, SnapShot Freeze 1 (SSF1). Patients after PCI and suspected of having ISR scheduled for high-resolution CCTA (randomly for 100 kVp low-dose CCTA or 120 kVp standard-dose) and invasive coronary angiography (ICA) were prospectively enrolled in this study. After the basic information pairing, a total of 105 patients were divided into the LD group (60 patients underwent 100 kVp low-dose CCTA reconstructed with DLIR and SSF2) and the SD group (45 patients underwent 120 kVp standard-dose CCTA reconstructed with ASIR-V and SSF1). Radiation and contrast medium doses, objective image quality including CT value, image noise (standard deviation), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) for the aorta, left main artery (LMA), left ascending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA) of the two groups were compared. A five-point scoring system was used for the overall image quality and stent appearance evaluation. Binary ISR was defined as an in-stent neointimal proliferation with diameter stenosis ≥50% to assess the diagnostic performance between the LD group and SD group with ICA as the standard reference. The LD group achieved better objective and subjective image quality than that of the SD group even with 39.1% radiation dose reduction and 28.0% contrast media reduction. The LD group improved the diagnostic accuracy for coronary ISR to 94.2% from the 83.8% of the SD group on the stent level and decreased the ratio of false-positive cases by 19.2%. Compared with standard-dose CCTA with ASIR-V and SSF1, the high-resolution, low-dose CCTA with DLIR and SSF2 reconstruction algorithms further improves the image quality and diagnostic performance for coronary ISR at 39.1% radiation dose reduction and 28.0% contrast dose reduction.

Stem cell collection and hematological recovery in the Fondazione Italiana Linfomi (FIL) MCL0208 clinical trial

In the frontline high-dose phase 3 FIL-MCL0208 trial (NCT02354313), 8% of enrolled mantle cell lymphoma (MCL) patients could not be randomised to receive lenalidomide (LEN) maintenance vs observation after autologous stem cell transplantation (ASCT) due to inadequate hematological recovery and 52% of those who started LEN, needed a dose reduction due to toxicity. We therefore focused on the role played by CD34 + hematopoietic stem cells (PBSC) harvesting and reinfusion on toxicity and outcome. Overall, 90% (n = 245) of enrolled patients who underwent the first leukapheresis collected ≥ 4 × 106 PBSC/kg, 2.6% (n = 7) mobilized < 4 × 106 PBSC/kg and 7.7% (n = 21) failed the collection. Similar results were obtained for the planned second leukapheresis, with only one patient failing both attempts. Median count of reinfused PBSC was 5 × 106/kg and median time to recovery from neutropenia G4 was 10 days from ASCT. No impact of mobilizing subtype or number of reinfused PBSC on hematological recovery and LEN dose reduction was noted. At a median follow-up of 75 months from ASCT, PFS and OS of transplanted patients were 50% and 73%, respectively. A long lasting G4 neutropenia after ASCT (> 10 days) was associated with a worse outcome, both in terms of PFS and OS. In conclusion, although the harvesting procedures proved feasible for younger MCL patients, long-lasting cytopenia following ASCT remains a significant issue: this can hinder the administration of effective maintenance therapies, potentially increasing the relapse rate and negatively affecting survival outcomes.

Impact of Simulated Reduced-Dose Chest CT on Diagnosing Pulmonary T1 Tumors and Patient Management.

To determine the diagnostic performance of simulated reduced-dose chest CT scans regarding pulmonary T1 tumors and assess the potential impact on patient management, a repository of 218 patients with histologically proven pulmonary T1 tumors was used. Virtual reduced-dose images were simulated at 25%- and 5%-dose levels. Tumor size, attenuation, and localization were scored by two experienced chest radiologists. The impact on patient management was assessed by comparing hypothetical LungRADS scores. The study included 210 patients (41% females, mean age 64.5 ± 9.2 years) with 250 eligible T1 tumors. There were differences between the original and the 5%-but not the 25%-dose simulations, and LungRADS scores varied between the dose levels with no clear trend. Sensitivity of Reader 1 was significantly lower using the 5%-dose vs. 25%-dose vs. original dose for size categorization (0.80 vs. 0.85 vs. 0.84; p = 0.007) and segmental localization (0.81 vs. 0.86 vs. 0.83; p = 0.018). Sensitivities of Reader 2 were unaffected by a dose reduction. A CT dose reduction may affect the correct categorization and localization of pulmonary T1 tumors and potentially affect patient management.

An Analysis of Computed Tomography Diagnostic Reference Levels in India Compared to Other Countries.

Computed Tomography (CT) is vital for diagnosing and monitoring medical conditions. However, increased usage raises concerns about patient radiation exposure. Diagnostic Reference Levels (DRLs) aim to minimize radiation doses in CT imaging. This study examines CT DRLs in India compared to other countries to identify optimization opportunities. A literature review was conducted to gather data from published studies, guidelines, and regulatory authorities. Findings show significant international variations in CT DRLs, with differences up to 50%. In India, DRLs also vary significantly across states. For head CT exams, Indian DRLs are generally 20-30% lower than international standards (27-47 mGy vs. 60 mGy). Conversely, for abdominal CT scans, Indian DRLs are 10-15% higher (12-16 mGy vs. 13 mGy). Factors influencing DRL variations include equipment differences, imaging protocols, patient demographics, and regulatory conditions. Dose-optimization techniques like automatic exposure control and iterative reconstruction can reduce radiation exposure by 25-60% while maintaining image quality. Comparative data highlight best practices, such as the United Kingdom's 30% reduction in CT doses from 1984 to 1995 via DRL implementation. This study suggests that adopting similar practices in India could reduce radiation doses by 20-40% for common CT procedures, promoting responsible CT usage and minimizing patient exposure.

Incidence of Fatigue Following Dexamethasone Administration for Supportive Therapy and Efficacy of Tapering in Perioperative Chemotherapy for Breast Cancer: A Retrospective Observational Study.

In perioperative chemotherapy for breast cancer, dexamethasone (DEX) is administered at high dose to prevent adverse effects. Abrupt cessation of high-dose DEX treatment induces fatigue, but the incidence of the fatigue is uncertain. In this study, we retrospectively evaluated the incidence of fatigue following DEX administration for supportive therapy and the improvement of fatigue with DEX tapering, a gradual reduction of the daily dose, in breast cancer patients. The subjects were 124 patients with breast cancer receiving epirubicin- or docetaxel-based regimens as perioperative chemotherapy. Of all patients, 16.1% of patients experienced fatigue after cessation of DEX administration. The severity of fatigue was grade 1 in 6.5% of patients, grade 2 in 8.1% of patients, and grade 3 in 1.6% of patients. There were no significant differences in dose and duration of DEX administration between the group with fatigue and the group without fatigue. In almost all patients with fatigue, DEX tapering was performed from the next cycle. The efficacy of DEX tapering was evaluated by comparing the grade and subjective symptoms. Following DEX tapering, the severity of fatigue was significantly reduced (p < 0.05), and the subjective symptom was improved in 94.7% of patients. Therefore, fatigue is occasionally induced after the cessation of DEX administration for supportive therapy in breast cancer patients. The tapering of DEX may be effective for fatigue.

Real‐world use of emicizumab in Chinese children with hemophilia A: Retrospective data from a comprehensive care center

ABSTRACTImportanceEmicizumab (EMI) is efficacious and safe for hemophilia A (HA) prophylaxis. However, its high cost poses a challenge in China.ObjectiveTo explore the possibility of using reduced‐dosage EMI in Chinese HA children.MethodsWe conducted a retrospective study for HA children in our Comprehensive Care Center. Data were collected pre‐ and post‐EMI treatment to evaluate bleeding rates. Laboratory analyses included factor VIII (FVIII)‐like activity and EMI concentration measurements.ResultsThirty‐four HA children receiving EMI prophylaxis for a median (range) 24.5 (2.5–47.9) months by June 2023. Of these, 25 (73.5%) were under 3 years of age, 26 (76.5%) had severe hemophilia and 12 (35.3%) were minimally treated or previously untreated patients. Thirty‐one (91.2%) of the 34 patients received reduced‐dosage EMI for economic reasons. EMI concentration and FVIII‐like activity measured showed a strong correlation. Overall, while on EMI, their annual treated bleeding rate (ATBR) and annual bleeding rate (ABR) decreased significantly (2–0) while their zero‐bleeding rate (ZBR) increased significantly (11.5%–65.4%). After 6 months of EMI, there was no significant difference in ATBR and ABR among various maintenance dosages. However, ZBR was significantly lower in dosages under 4 mg/kg (P = 0.0156). Receiver operator characteristic curves suggested the following cutoff values for zero bleeding: EMI 4‐weekly maintenance dosage 3.8 mg/kg, EMI concentration 48.1 μg/mL, and FVIII‐like activity 15.4 IU/dL.InterpretationWe showed EMI effectively prevented bleeding even at reduced dosages. However, the bleeding risk may be higher with EMI 4‐weekly maintenance dosage &lt;3.8 mg/kg, EMI concentration &lt;48.1 μg/mL, and FVIII‐like activity &lt;15.4 IU/dL for zero bleeding. It is important that dosage reduction be done rationally. Dosage tailoring is possible.

Applicability and potential of monitored reconstruction in computed tomography.

Monitored tomographic reconstruction (MTR) is a potentially powerful tool for dose and time reduction in computed tomography scanning. We are the first to study the issue of practical implementation of MTR protocols in current-generation real-life instruments. We propose an empirical quantitative model for calculating acquisition and reconstruction times. It is demonstrated that projection acquisition order has a significant impact on the time and dose of tomographic experiments. The new alternative acquisition most suitable for MTR protocols is proposed. To estimate the restrictions and scope of applicability for MTR four typical commercial setups are studied within a proposed model. We construct an experimental stand for achieving a real-time reconstruction, together with validation of the proposed acquisition time model. We demonstrate that real-time reconstruction may be implemented without slowing down an acquisition process. An optimization of reconstruction from partial data is proposed, which allowed the production of 385 and 440 reconstructions for standard and proposed acquisition orders correspondingly during a single acquisition of 512 projections. The results of the study demonstrate that with proposed optimizations MTR can be effectively utilized for practical applications using the current generation of existing setups in industrial and nano tomography fields.

Biopsy-proven BK virus nephropathy inrenal transplant recipients: A-multi-central study from Turkey (BK-TURK STUDY).

BK polyomavirus infection is a challenging complication of renal transplantation. The management is not standardized and is based on reports from transplantation centers' experiences, usually with small sample sizes. Therefore, we aimed to present our countrywide experience with BK virus nephropathy (BKVN) in renal transplant recipients. Our study was carried out with the participation of 30 transplantation centers from all regions of Turkey. Only cases with allograft biopsy-proven BKVN were included in the study. 13,857 patients from 30 transplantation centers were screened, and 207 BK nephropathy cases were included. The mean age was 46.4± 13.1 years, and 146 (70.5%) patients were male. The mean time to diagnosis of BK nephropathy was 15.8±22.2 months after transplantation. At diagnosis, the mean creatinine level was 1.8± 0.7 mg/dL, and the mean estimated glomerular filtration rate was 45.8 ± 19.6 mL/min/1.73m2 . In addition to dose reduction or discontinuation of immunosuppressive drugs, 18 patients were treated with cidofovir, 11 patients with leflunomide, 17 patients with quinolones, 15 patients with intravenous immunoglobulin (IVIG), 5 patients with cidofovir plus IVIG, and 12 patients with leflunomide plus IVIG. None of the patients receiving leflunomide or leflunomide plus IVIG had allograft loss. During follow-up, allograft loss occurred in 32 (15%) out of 207 patients with BK nephropathy. BKVN is still a frequent cause of allograft loss in kidney transplantation and is not fully elucidated. The results of our study suggest that leflunomide treatment is associated with more favorable allograft outcomes.

Modeling Plutonium Decorporation in a Female Nuclear Worker Treated with Ca-DTPA after Inhalation Intake.

The present work models plutonium (Pu) biokinetics in a female former nuclear worker. Her bioassay measurements are available at the US Transuranium and Uranium Registries. The worker was internally exposed to a plutonium-americium mixture via acute inhalation at a nuclear weapons facility. She was medically treated with injections of 1 g Ca-DTPA on days 0, 5, and 14 after the intake. Between days 0 and 20, fecal and urine samples were collected and analyzed for 239Pu and 241Am. Subsequently, she was followed up for bioassay monitoring over 14 y, with additional post-treatment urine samples collected and analyzed for 239Pu. The uniqueness of this dataset is due to the availability of: (1) both early and long-term bioassay data from a female with plutonium intake; (2) data on chelation therapy for a female; and (3) fecal measurement results. Chelation therapy with Ca- and/or Zn-salts of DTPA is known to aid in reducing the internal radiation dose by enhancing the excretion of plutonium and americium from the body. Such enhancement affects plutonium biokinetics in the human body, posing a challenge to the internal dose assessment. The current radiation dose assessment practice is to exclude the data affected by Ca-DTPA from the analysis. The present analysis is the first to explicitly model the chelation-affected bioassay data in a female by using a newly developed chelation model. Thus, the bioassay data collected during and after the Ca-DTPA administrations were used for biokinetic modeling and dose assessment. The Markov Chain Monte Carlo method was used to investigate model parameter uncertainty, based on the bioassay data and assumed prior probability distributions. A χ2/nData (number of data points) ≈ 1 was observed in this study, which indicates self-consistency of the data with the model. Results of this study show that the worker's 239Pu intake was 12 Bq, with a committed effective dose to the whole-body of 1.2 mSv and a committed equivalent dose to the bone surfaces, liver, and lungs of 37.8, 9.1, and 0.8 mSv, respectively. This study also discusses the worker's dose reduction due to chelation treatment.

Therapeutic Modulation of Dupilumab in Patients with Severe Atopic Dermatitis: Clinical Effectiveness in Real Life.

Background: De-escalation strategies have become increasingly used in the treatment of atopic dermatitis (AD) patients with dupilumab. Dose spacing (DS) refers to dose reduction by dosage elongation strategies from 2 to 8 weeks between dupilumab injections, in patients with stable response to treatment or affected by numerous adverse events. Objectives: Investigate safety and clinical effectiveness of DS strategy in AD patients treated with dupilumab. Methods: A retrospective cohort study was conducted on AD patients aged ≥18 years treated with dupilumab undergoing DS. Pre-post analyses were conducted on this cohort, termed cohort A, between effectiveness outcomes at baseline, at 16 weeks of treatment, at the index date identified as the mean follow-up time between dupilumab initiation and DS, and at subsequent two follow-up visits: T1 and T2. Based on the index date, a cohort B of AD patients on dupilumab treatment not experiencing DS was then compared with cohort A for the same outcomes at the same time points. Results: Seventy-three out of 452 patients treated with dupilumab underwent DS. The mean time since treatment initiation was 28.6 months. Mean Eczema Area Severity Index (EASI) from the index date remained stable until the second follow-up visit (T2) 0.2-0.8 with no significant pre-post differences (P > 0.05). Similar considerations can be made for mean number rating scale worst pruritus (NRSp), numerical rating scale disturbs of sleeping/sleeping disturb (NRSsd), mean Dermatology Life Quality Index (DLQI), and EASI Head and Neck. Attainment of relative outcomes remained stable for EASI75, 90, ≤ 7, DLQI ≤ 5, and NRSp ≤ 4. When compared with cohort B, no clinically significant differences were observed in mean reductions in all outcomes analyzed. Conclusions: DS in our study appears to be an effective and safe strategy in treating patients with severe AD after the initial therapeutic response.

Radiotherapy for subependymal giant cell astrocytoma: time to challenge a historical ban? A case report and review of the literature

BackgroundSubependymal giant cell astrocytoma is a benign brain tumor that occurs in patients with tuberous sclerosis complex. Surgical removal is the traditional treatment, and expert opinion is strongly against the use of radiotherapy. Recently, success has been reported with the mTor inhibitor everolimus in reducing tumor volume, but regrowth has been observed after dose reduction or cessation.Case reportWe present the case of a 40-year-old Asian female patient treated successfully for growing bilateral subependymal giant cell astrocytoma with fractionated stereotactic radiotherapy before everolimus became available. After a follow-up of 8 years, everolimus was administered for renal angiomyolipoma and the patient was followed up until 13 years after radiotherapy. Successive magnetic resonance imaging demonstrated an 80% volume reduction after radiotherapy that increased to 90% with everolimus. A review of the literature was done leveraging Medline via PubMed, and we assembled a database of 1298 article references and 780 full-text articles in search of evidence for contraindicating radiotherapy in subependymal giant cell astrocytoma. Varying results of single-fraction radiosurgery were described in a total of 13 cases. Only in two published cases was the radiation dose of fractionated radiotherapy mentioned. One single publication mentions an induced secondary brain tumor 8 years after whole-brain radiotherapy.ConclusionThere is no evidence of contraindication and exclusion of fractionated radiotherapy in treating subependymal giant cell astrocytoma. Our experience demonstrates that subependymal giant cell astrocytoma, as other benign intracranial tumors, responds slowly but progressively to radiotherapy and suggests that fractionated stereotactic radiotherapy holds promise to consolidate responses obtained with mTor inhibitors avoiding regrowth after cessation.

Improvement of treatment plan quality with modified fixed field volumetric modulated arc therapy in cervical cancer.

This study aims to introduce modified fixed field volumetric modulated arc therapy (MF-VMAT) which manually opened the field size by fixing the jaws and comparing it to the typical planning technique, auto field volumetric modulated arc therapy (AF-VMAT) in cervical cancer treatment planning. Previously treated twenty-eight cervical cancer plans were retrospectively randomly selected and replanned in this study using two different planning techniques: AF-VMAT and MF-VMAT, resulting in a total of fifty-six treatment plans. In this study, we compared both planning techniques in three parts: (1) Organ at Risk (OARs) and whole-body dose, (2) Treatment plan efficiency, and (3) Treatment plan accuracy. For OARs dose, bowel bag (p-value=0.001), rectum (p-value=0.002), and left femoral head (p-value=0.001) and whole-body (p-value=0.000) received a statistically significant dose reduction when using the MF-VMAT plan. Regarding plan efficiency, MF-VMAT exhibited a statistically significant increase in both number of monitor units (MUs) and control points (p-values=0.000), while beam-on time, maximum leaf travel, average maximum leaf travel, and maximum leaf travel per gantry rotation were statistically significant decreased (p-values=0.000). In terms of plan accuracy, the average gamma passing rate was higher in the MF-VMAT plan for both absolute dose (AD) (p-value=0.001, 0.004) and relative dose (RD) (p-value=0.000, 0.000) for 3%/3 and 3%/2mm gamma criteria, respectively. The MF-VMAT planning technique significantly reduces OAR doses and decreases the spread of low doses to normal tissues in cervical cancer patients. Additionally, this planning approach demonstrates efficient plans with lower beam-on time and reduced maximum leaf travel. Furthermore, it indicates higher plan accuracy through an increase in the average gamma passing rate compared to the AF-VMAT plan. Consequently, MF-VMAT offers an effective treatment planning technique for cervical cancer patients.

Preparation and In-Vitro Characterization of Solid Lipid Nanoparticles Containing Artemisinin and Curcumin.

Malaria remains a formidable public health obstacle across Africa, Southeast Asia, and portions of South America, exacerbated by resistance to antimalarial medications, such as artemisinin-based combinations. The combination of curcumin and artemisinin shows promise due to its potential for dose reduction, reduced toxicity, synergistic effects, and suitability for drug delivery improvement. This research aims to enhance the solubility and dissolution rates of curcumin and artemisinin by employing Solid Lipid Nanoparticles (SLNs). Oral delivery of both drugs faces challenges due to their poor water solubility, inefficient absorption, and rapid metabolism and elimination. The study focuses on formulating and optimizing Solid Lipid Nanoparticles (SLNs) encapsulating artemisinin (ART) and curcumin (CUR). SLNs were developed using the hot homogenization method, incorporating ultrasonication. Drug-excipient compatibility was evaluated using Differential Scanning Calorimetry (DSC). Lipid and surfactant screening was performed to select suitable components. A 3² full factorial design was utilized to investigate the influence of lipid and surfactant concentrations on key parameters, such as entrapment efficiency (%EE) and cumulative drug release (%CDR). Additionally, evaluations of % entrapment efficiency, drug loading, particle size, zeta potential, and in-vitro drug release were conducted. Successful development of artemisinin and curcumin SLNs was achieved using a full factorial design, demonstrating controlled drug release and high entrapment efficiency. The optimized nanoparticles exhibited a size of 114.7nm, uniformity (PDI: 0.261), and a zeta potential of -9.24 mV. Artemisinin and curcumin showed %EE values of 79.1% and 74.5%, respectively, with cumulative drug release of 85.1% and 80.9%, respectively. The full factorial design indicated that increased lipid concentration improved %EE, while higher surfactant concentration enhanced drug release and %EE. Stability studies of the optimized batch revealed no alterations in physical or chemical characteristics. The study successfully developed Solid Lipid Nanoparticles (SLNs) for artemisinin and curcumin, achieving controlled drug release, high entrapment efficiency, and desired particle size and uniformity. This advancement holds promise for enhancing drug delivery of herbal formulations.

Key Component Analysis of the Time Toxicity Interaction of Five Antibiotics to Q67.

Antibiotics are considered as persistent emerging contaminants. The phenomenon of mixed exposure to the environment is a common occurrence causing serious harm to human health and the environment. Therefore, we employed enrofloxacin (ENR), chlortetracycline (CTC), methotrexate (TMP), chloramphenicol (CMP), and erythromycin (ETM) in this study. Nine treatments were designed using the uniform design concentration ratio (UDCR) method to systematically determine the toxicity of individual contaminants and their mixtures on Vibrio qinghaiensis sp.-Q67 through the time-dependent microplate toxicity assay. The combinatorial index (CI) method and the dose reduction index (DRI) were used to analyze the toxic interactions of the mixtures and the magnitude of the contribution of each component to the toxic interactions. The results showed that the toxicities of ENR, CTC, TMR, CMP, and ETM and their mixtures were time-dependent, with toxic effects being enhanced except when exposure time was prolonged. The types of toxic interactions in the ENR-CTC-TMR-CMP-ETM mixtures were found to be correlated with the proportion of each component's concentration, where the proportion of the components exerted the most significant influence. Through DRI extrapolation, it was determined that the primary components of the mixture exhibited a pronounced dependency on time. Specifically, at the 4 h mark, TMP emerged as the predominant component, gradually giving way to ENR as time advanced. Upon analyzing the frequency of mixture interactions under specified effects, the additive effect appeared most frequently (66.6%), while the antagonist effect appeared the least frequently (15.9%) among the nine rays.

The liminal space of first-episode psychosis and its treatment: A qualitative study exploring the experience of young people participating in an antipsychotic dose reduction randomized controlled trial.

The current guidelines recommend continuation of antipsychotic medication for a minimum of at least 1 year following a first episode of psychosis (FEP). There have been several trials investigating whether early dose reduction or cessation leads to improved functional outcomes. The aim of this study was to explore the experience of consenting to and participating in a randomized controlled trial (RCT) of antipsychotic medication cessation. Five participants in the Reduce trial-an RCT evaluating early antipsychotic medication dose reduction/cessation following FEP-aged 22-24 years completed a semistructured qualitative interview following the RCT. Interpretive phenomenological analysis was undertaken to understand the key themes. A superordinate theme was derived from interviews: the Liminal Space of FEP and treatment. Themes within the Liminal Space included: rejection versus identification with psychosis, medication as symbolic of illness versus wellness, embodiment of wellness and illness with medication, medication as symbolic of independence versus dependence, discovery of independence when autonomously choosing medication, the Reduce trial offered safety to navigate the liminal space, and self-exploration versus altruism. The experience and treatment of FEP involves young people feeling torn between multiple, competing perspectives, demands, and priorities. Participation in an RCT exploring dose reduction provided additional supports contributing to the perception of greater safety to navigate their own experiences of treatment that was appropriate for them. When treatment is experienced as collaborative, involves shared decision making and support, other than medication, young people feel more equipped to navigate the liminal space. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Examining the impact of age on chemotherapy completion in epithelial ovarian, fallopian tube and primary peritoneal cancer: a retrospective cohort study in Thailand

ObjectiveTo explore the difference in chemotherapy completion and reasons for discontinuation between older (≥70 years) and younger (<70 years) patients.DesignRetrospective cohort study.SettingSingle tertiary centre in Thailand.ParticipantsThe patients who received chemotherapy...

Achievement of deep molecular response and treatment-free remission with asciminib treatment in CML.

We evaluated the possibility of treatment-free remission (TFR) and durability of deep molecular response (DMR) with asciminib treatment by monitoring major BCR::ABL mRNA on the International Scale (BCR::ABL-IS) in 4 patients who needed to reduce or discontinue asciminib due to adverse event concerns, intolerance, or personal circumstances. IS increased in all 4 patients after discontinuation of asciminib, but 3 patients who resumed asciminib achieved DMR again. None of the patients achieved TFR with asciminib, but DMR could be achieved again by restarting asciminib after TFR failure. As this was a retrospective study in a small number of patients, no conclusions can be drawn regarding the possibility of TFR with asciminib. However, this study included patients with short treatment duration and DMR maintenance periods, so strict conditioning may be necessary. Safe dose reduction or TFR with asciminib may need to be considered in more cases.